This stunning discovery about the brain will have scientists rewriting textbooks

Antoine Louveau, a
post-doctoral researcher, peered into a microscope and noticed
something strange.Courtesy University
of Virginia

Antoine Louveau was looking through his microscope at thin
membranes that protect the brain when he saw something that
absolutely shouldn't be there: a lymphatic vessel.

The lymphatic system is part of the circulatory system but,
instead of blood, it carries lymph — a clear liquid that ferries
immune cells and rids the body of toxins and waste. As a 2009
research review notes, it is "an undisputed
anatomical fact" that the brain is the only major organ that
lacks a direct connection to the lymphatic system.

Now that claim is disputed. If confirmed, the discovery
may have huge implications for studying brain diseases like
Alzheimer's and multiple sclerosis (MS).

"All the textbooks said there were not supposed to be any
lymphatic vessels in that area," said Louveau, a post-doctoral
researcher at the University of Virginia. But after he and UVA
neuroscientist Jonathan Kipnis ran a battery of tests, they
discovered Louveau had been right. "It was exactly what we
thought it couldn't be," Louveau said.

The elusive lymphatic vessel hid in plain sight, throughout
decades of research, because it was very small and tucked behind
a major blood vessel.

Experts greeted
the resulting study, published Monday in the journal Nature,
with a mixture of excitement and caution. The main hurdles: Other
researchers must replicate the work and confirm the vessel exists
in humans, since the study primarily examined mouse brains.

The old map of the
lymphatic system, left, which didn't connect to the brain, and
the updated map based on the new discovery.Courtesy University of Virginia

Staci
Bilbo, a Duke University neuroscientist who studies
connections between the brain and the immune system, wasn't
involved in the study but quickly heard about it when several
colleagues emailed her. "It's generating quite a bit of
excitement in the field," she said.

Maiken Nedergaard, a neuroscientist at the University of
Rochester Medical Center who discovered
a related system in the brain in 2012
(and also wasn't involved in the work) said she was "pretty
excited" but "not awfully surprised."

Still, Nedergaard said the implications for diseases involving
the brain and the immune system — not only Alzheimer's and MS,
but also meningitis — could be significant. "It gives us a new
tool," she said. "In biology and medicine, if you understand
something, you [can start to] find new targets for treatments."

Immune system cells
(T-cells) are shown in red; the lymphatic vessel is shown
blue.Courtesy University of
Virginia

Scientists used to think that the brain was totally cut off from
the immune system and that if immune cells were found there,
"something was going wrong," Kipnis
told The Scientist.

Work by Nedergaard and others has changed that in recent years,
but a lot of confusion about how the brain and the immune system
communicated remained, since there seemed to be no direct access.
How did immune cells get in, and how did they leave? No one knew.

The new study stands to resolve this and lead to new
understanding of and treatments for vexing diseases.

Take multiple sclerosis, for example, a mysterious
ailment that affects about 2.3 million people worldwide. Many researchers
believe whatever triggers its attacks on nerves in the spine,
brain, and eye starts in the body and somehow moves to the brain,
Bilbo said. "This [discovery] suggests MS might actually start in
the brain," she said. "It reverses our understanding of that
pathology."

Then there are neurodegenerative diseases like Alzheimer's. The
new vessel might be a good place to look for something going
wrong. "In Alzheimer's, there are accumulations of big protein
chunks in the brain," Kipnis said in
a statement. "We think they may be accumulating in the brain
because they're not being efficiently removed by these vessels."

That's just speculation — an intriguing possibility Kipnis,
Louveau, and most likely others will explore in future studies.
The brain's newfound lymphatic drainage system, and all the
possible ways it can malfunction, may well be critical in these
diseases. But there's also a chance at this early stage
of research that it's a red herring: an interesting anatomical
finding that's exciting for scientists but leads to little for
patients.

For now, the researchers are hard at work on two major follow-up
questions to try to figure out how the research might be relevant
and useful. First, does this system definitely exist in humans?
And second, what is the potential role of these vessels in
Alzheimer's, MS, and meningitis?

The lymphatic vessels are
shown in red, almost invisible beside the blood vessels (in
green).Courtesy University of
Virginia

Other scientists will scramble to replicate the results and build
on the finding. If the discovery holds up, it could open a number
of exciting new avenues for research.

Bilbo said, for example, there has hardly been any research on
the brain's "portal areas" — those foggy zones where the brain
connects to yet is shielded from the rest of the body. "[These
are] really underexplored parts of neuroscience and neurology ...
[These] pathways are really misunderstood. Not even
misunderstood, but ignored."

The idea that an entire part of the lymphatic system was hiding
in plain sight should ensure that these potentially crucial areas
are ignored no longer. With any luck, this might help us solve
more mysteries behind the brain — and fight some of its greatest
foes.